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Asepsis, clean air and plastics

The Pharmaceutical Journal Vol 265 No 7128p931-932
December 23/30, 2000 Christmas miscellany

By C. V. Hammond, FRPharmS

My article “Wounds and the’Magic Balsam’” last year described the work that Smith & Nephew did in 1950 leading to balsam of Peru being removed from the British Pharmaceutical Codex monograph on paraffin gauze dressing.1 Although clean air cabinets or rooms were used in bacteriology they were not readily available at that time and manufacture of other particle sensitive equipment such as electronic microcircuitry would not become widespread until 20 years later.
My own work was influenced by a tragic event in Canada in about 1949, caused by the application of plaster casts to a compound fracture that had been caused in a road accident. Normally splints would have been applied to unbroken or sealed skin surfaces. In the Canadian case the injuries were so severe that the plaster was in contact with open wounds. The patient died, but it was thought that, even with sterile treatment, the victim could not have survived. However, the post mortem examination made it clear that a tetanus infection was the cause of death. Furthermore, the plaster of Paris in the bandages used in Canada was found to contain tetanus spores. Fortunately Smith&Nephew had not made the product, but the board called an emergency meeting of all concerned in order to see what could be done to make Gypsona a sterile product and to review the bacteriological state of the other products.


Smith&Nephew did not have a bacteriology section in the laboratory then, and samples of all of the materials used to manufacture and pack Gypsona bandages were sent to a commercial laboratory for test. We were horrified by the results showing the presence of masses of tetanus organisms in both the plaster of Paris and the perforated cardboard cores on to which the bandages were wound. Because the main sterilisation processes for pharmaceutical and surgical products at the time involved either steam or high temperatures, this raised the problem of what could be done to sterilise Gypsona plaster of Paris bandages. Steam treatment would cause them to set and become useless. Efficient heat treatment would damage the cotton and adhesive, rendering both unsightly and useless.
At that time the laboratory staff consisted of the chief chemist, Donald Burley, and me as works pharmacist and assistant chief chemist. The remaining staff consisted of Peter Bricklebank, who was an undergraduate studying chemistry, and six laboratory assistants with various capabilities. One of the latter had worked previously for a year or two in Reckitt&Colman?s Hull laboratory and another one with one of the fish oil refinery laboratories. I was the only employee with bacteriological training, although there was a company consultant hospital pharmacist, Mr Llewelyn Jones, who was present at the meeting. I suggested that we should be able to use a bactericidal compound to kill off the spores in the plaster, that the supporting bandage could be made from sterilised material, and that the cores could be made from bacteriologically “clean”metal, or one of the new plastics. Llewelyn Jones suggested testing a number of the, then new, quaternary ammonium bactericides that would not react with the remaining materials.
At the same time, I had the idea that a bactericidal plasticiser could be used in the production of self-sterile plastic cores. The firm?s purchasing manager was of the opinion that these would be ruled out on grounds of cost, and he quoted the extremely cheap price of the existing perforated cardboard cores. Nevertheless I was given permission to investigate the problem of using plastics. My first quest was for plastic cores that were similar in design to the existing cardboard ones. It so happened that similar articles were being produced for use as hair curling rollers in home perm kits, etc. The purchasing department obtained some of these for me, although they cost at least six times the price of the cardboard ones.
While this was being investigated, Llewelyn Jones had performed tests, which showed that the quaternary compounds could sterilise the plaster, when used in the slurry mixing process.
A meeting was then called to discuss the core sterilisation problem. In my early days in the laboratory, I had become familiar with plastic polymer formulation through technical meetings between the engineers and the laboratory concerning conditions for manufacturing what was to be known as Waterproof Elastoplast. The base film for this was manufactured from a thermoplastic co-polymer using large heated friction mixing and extrusion rollers. Now my task was to learn much more about the various forms of new plastic materials and the methods by which products made from them were manufactured.
I pointed to the fact that the available hair rollers were made by an injection moulding process. If we could produce a cross section design which was suitable for extrusion, and on to which a bandage could be wound, then the cost of production was almost solved. One problem associated with this idea was that the core had to be designed to allow water to flow easily into the spooled bandage in use. At this juncture Karl Dolezalek handed me a paper on which he had drawn a cross. My immediate reaction was that he must be suggesting divine help, until he explained that the cross was the simplest form which could be fitted into a spindle with a mating slot and then used to wind filaments or strips. On removal from the winding spindle there would still be channels through which water could flow in use. Three-ribbed extrusions would do the job, but the finished product would be triangular, inelegant and difficult to unroll in use. More than four ribs used more material and provided less space for the water to circulate in use.


Since one of my responsibilities was the technology of packaging, I was deputed to investigate the idea. Extrusion dies, called “soft tools”, can be used for experimental production runs of limited duration. With the help of the main plastics extrusion compound manufacturers I was able to obtain test lengths of extruded cruciform-section rigid plastic materials, which were sterile as they emerged from the extruder. Some of the spooling machines used for Gypsona bandages were fitted with slotted spindles. Initially, the extruded cruciform core section was cut into pieces the same length as the width of the production bandage. It was soon obvious that, in spite of the rounded beads on each fin of the section, the sharp rectangular corners of the cut cores were snagging the edges of the bandages. This was overcome by trimming the corners to round them off.
Eventually, the cost of the new cores was reduced to a quarter of that of the old perforated cardboard tubes. Another saving was made by the large quantity of off-cuts from the trimming process being granulated and returned to the extrusion process, making the waste material negligible. A patent was applied for for this type of plastic core on May 23, 1949.2 While work on the cores was going on, the then new domiphen bromide bactericide was added to the slurry mix, and we were able to produce bandages which were rendered clean and tetanus free, but not completely sterile. Sterility was something that had to wait a few years until suitable radiation sterilisation came into being. Sending samples to outside laboratories for sterility tests was expensive, time-consuming and inefficient. Donald Burley discussed the feasibility of setting up our own bacteriology testing section in a sealed off area intended for that purpose within the new laboratory. I had not performed any sterility tests since before the war when, as a student I had been shown the technique of producing sterile nutrient media in Petri dishes and test tubes. Swabs and sterile platinum wires had been used to obtain test samples that were introduced to the media and incubated at body temperature for 24 hours or until colonies of organisms could be seen. Suitable specimens were applied to slides and then examined under the microscope.I explained the necessity for “clean air”being pumped into the sterility testing laboratory, producing positive air pressure to prevent the ingress of contamination from outside, etc. But there was a principle of not spending money on purpose designed specialist equipment.
The chief engineer was able to obtain an ex-Navy air filter in an Admiralty surplus sale. This had been used to filter air in submarines during the 1939-45 war and it looked as though it would provide a good start to our experiments. Prior to the start of the war there had been great concern in Britain about the number of naval cadets who developed and died from rheumatic fever. The Royal Navy medical branch used the Bordet-Gengou slit sampler, “mouth to slit”method whereby air was sucked through a standard slit on to a Petri dish containing nutrient media. The number of bacteria was estimated from the number of organisms that developed on the plate after incubation. This same test was used those days to take samples in local cinemas, etc (R. Mackenzie, 1999, quoted in personal communication from Edwin Jenkins).
There is a reference to the Bordet-Gengou “cough test”in the 1938 edition of Martindale II on p807 under the heading “Whooping cough”, and in researching for details of this I came across an invaluable publication on studies in air hygiene3 in the Pharmaceutical Society?s library. This describes improvements that had been developed by R. B. Bourdillon (1888-1971).
By 1950, a Casella airborne bacteria sampler was available commercially and I used one of these of samplers in our many experiments. The techniques used were those that are described in the studies in air hygiene. These involved experiments with various filters, disinfecting chemical aerosols (mainly with propylene glycol) and ultraviolet lamps arranged within the filter unit. Details of the efficiency of this type of sampler were published later in the ongoing work of R. B. Bourdillon.4


The small bacteriology laboratory, from memory, was approximately 15ft (4.6m) long, 12ft (3.6m) wide with a ceiling height of 10ft (3m). It was sealed off from the main laboratory and provided with a positive air pressure from an electric fan-driven filter unit. There was an additional air “sterilisation”unit situated within this area that was used for the work inside this laboratory that contained the necessary aseptic working cabinet. With all of these precautions it was possible to reduce the bacterial count using the slit sampler
Recently I had email correspondence with Professor Antony Bourdillon (visiting professor, department of materials science, National University of Singapore) questioning him as to whether he was related to R. B. Bourdillon. He replied: “Funny that you should mention Robert Benedict Bourdillon. I never met him but on my first day in the Clarendon laboratory in the 60s, the photographer said he had known three generations of my name. The first was Robert and the second his son. Both, as I soon learned, were well known in both Oxford and elsewhere. My father?s grandfather was brother to Robert?s grandfather. According to the family tree, Robert was born on September 8, 1888. He went to Balliol college, married Harriet Barnes in 1922 and died in 1971 in B.C. [possibly British Columbia] with an MC and AFC. He had two sons Thomas Duncan and William. The Times printed an obit. Unfortunately your slit sampler was not the only thing Robert invented. When the same Thom was supposed to make the final assault on Everest he was wearing breathing apparatus designed by his father. It iced up and he fell back unsuccessfully to camp roped to his climbing partner, Dr Evans, exhausted and sliding on the ice and snow. Hilary and Tensing took the summit next day in time for the coronation in 1953. Thom was unhappily killed subsequently in a climbing accident in the Alps in 1956 leaving his wife Jennifer Thomas with two small children Nicola and Simon. A contemporary of his at the Clarendon told me that he was expert in the flow of gases and worked for the Ministry of Defence.”
In consultation with the engineers and with board approval, we purchased a submarine air filtration unit at an Admiralty war surplus sale, such sales being very common after the war.
George Leavey, a director of the senior S&N Associated Companies board in London was very interested in these developments. He happened to call into the Hull laboratory in the middle of these investigations. At a time I was using a war surplus ex-RAF aerial photography camera that I had adapted to enlarge slides showing the setting stages of the plaster of Paris that we were using at that time. At the same time the results could be photographed. He was very intrigued with this, and asked me whether I needed any special equipment that might be expensive. A good microscope was the main item in my list, and he happened to have one in a company that his son managed. The apparatus had been used in connection with their manufacture of Litz wires. He was sure that it was not being used, it could be available immediately, but in any case a new one could be purchased for us if the Litz wire firm needed theirs returning.
In more recent years “clean air benches”have become available for localised sterile procedures, but in those year immediately after the war they were neither compact nor readily available.
When the sterility laboratory was almost ready for use, I was able to carry out some tests with UV lights installed in the filter ducting. This had the effect needed, judged by the Bourdillon test results showing levels of organisms in the air being reduced to an acceptable figure in the test room. The use of an enclosed cabinet with protected entry for handling samples completed our requirements and enabled us to begin tests.


George Leavey eventually brought the fine binocular microscope to me in person. Its main use was to be for the examination and recognition of bacteria and fungi that developed on our test plates. From the results of our tests on the new components and finished Gypsona bandages we were pleased to note that we had a product that was almost sterile, but in any case it was free from harmful spores, such as the Clostridium tetani one.
With much safer bandages and cores there was one other important aspect to be tackled, namely the packaging in which the bandages would be sealed. This had to provide protection against absorption of moisture from the atmosphere or ingress of water in other circumstances. A suitable package was made using another new plastic material ? polyethylene ? but that is another story that eventually led to the formation of Smith & Nephew plastics firm.
Since those days particle accelerators have improved and the development of the Van der Graaff electrostatic generator resulted in sterilisation techniques that could be used with heat and moisture sensitive pharmaceutical and other products. More sophisticated electronic techniques are now readily available, but many of the older, and in my view more exciting experiments would be considered as simple.


1.Hammond CV. Wounds and the magic balsam. Pharm J 1999;263-992-3.
2.Patent Specification 686,449. Improvements in and relating to Medical or Surgical Bandages, Karl Martin Dolezalek, Donald Weston Burley and Charles Victor Hammond. Filed May 23, 1950. Complete specification published January 28, 1953.
3.Bourdillon RB, Lidwell OM, Lovelock JE. Studies in air hygiene, Medical Council, Special Report Series No. 262 London: HM Stationery Office; 1948.
4.Bourdillon RB, Lidwell OM, Thomas, John C. A slit sampler for collecting and counting air-borne bacteria. J Hygiene 1941;41:197.

Mr Hammond is a pharmacist, now retired, from Southport, Merseyside

Citation: The Pharmaceutical Journal URI: 20003897

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